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Published on: December 5, 2020
Antifungal Mechanism Effect of Artemisinin on Fusarium solani
César Espinoza1, Francisco Roberto Quiroz-Figueroa2, Oswaldo Guzmán-López3
1Centro de Investigación en Micología Aplicada, Universidad Veracruzana, Médicos 5, Unidad del Bosque, Xalapa-Enríquez 91010, Mexico.
Abstract:
Background:Fusarium solani (Fs), a drug-resistant phytopathogenic fungus, is a major cause of severe infections in both plants and humans. Artemisia annua and its derivatives exhibit antimicrobial, antiviral and anticholesterolemic activities, yet their clinical use has been dominated by potent antimalarial and anticancer effects. Artemisinin (ART), a sesquiterpene lactone isolated from A. annua, is well recognized for its antimalarial efficacy but remains underexplored as an antifungal agent. Methods: Conidia of Fs were treated with increasing concentrations of ART (75-500 μM) for 0 and 24 h. Fungal viability was assessed using viability assays. Membrane permeability was examined using confocal laser scanning microscopy with propidium iodide (PI) staining. Protein carbonylation assays were performed to quantify oxidative damage induced by ART. Results: A 24 h, ART exposure reduced Fs viability in a dose-dependent manner, with an IC50 of 147.5 μM. At 500 μM, ART achieved fungicidal activity with 99% growth inhibition. Confocal microscopy confirmed extensive membrane disruption in ART-treated conidia, while carbonylation assays demonstrated marked protein oxidation, supporting a mechanism involving free radical generation from the peroxide bridge of ART. ART exhibits potent antifungal activity against Fs, mediated by oxidative stress, membrane disruption and protein carbonylation. Conclusions: These findings highlight ART as a promising candidate for antifungal drug development against resistant Fusarium species.
Insights
Artemisinin (ART), derived from Artemisia annua, shows potent antifungal activity against drug-resistant Fusarium solani. ART disrupts fungal membranes and causes protein oxidation, offering a new avenue for antifungal drug development.
Area of Science:
- Mycology
- Pharmacology
- Medicinal Chemistry
Background:
- Fusarium solani (Fs) is a drug-resistant fungus causing severe plant and human infections.
- Artemisia annua derivatives possess antimicrobial properties, but Artemisinin (ART) is primarily known for antimalarial and anticancer effects.
- Artemisinin's antifungal potential against Fusarium species remains largely unexplored.
Purpose of the Study:
- To investigate the antifungal activity of Artemisinin (ART) against Fusarium solani (Fs).
- To elucidate the mechanism of action of ART against Fs, focusing on membrane integrity and oxidative stress.
Main Methods:
- Fs conidia were exposed to varying concentrations of ART (75-500 μM) for 24 hours.
- Fungal viability was assessed using viability assays.
- Membrane permeability and protein carbonylation were analyzed using confocal microscopy and carbonylation assays, respectively.
Main Results:
- ART demonstrated dose-dependent antifungal activity, with an IC50 of 147.5 μM and 99% growth inhibition at 500 μM.
- Confocal microscopy revealed significant membrane disruption in ART-treated Fs conidia.
- Protein carbonylation assays indicated oxidative damage, suggesting ART generates free radicals.
Conclusions:
- Artemisinin exhibits potent antifungal activity against Fusarium solani.
- The mechanism involves oxidative stress, leading to membrane disruption and protein carbonylation.
- ART presents a promising candidate for developing new antifungal drugs against resistant Fusarium species.
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